Effect of Chronic Amiodarone Therapy on Defibrillation Energy Requirements in Humans

INTRODUCTION: The effect of oral amiodarone therapy on defibrillation energy requirements in patients with an implantable defibrillator has not been established. METHODS AND RESULTS: Twenty-one consecutive patients with implantable biphasic waveform defibrillators underwent a step-down determination of the defibrillation energy requirement 211 +/- 12 days before and 73 +/- 22 days after initiation of amiodarone therapy (mean total dose 26.7 +/- 11.1 g). Serum amiodarone and desethylamiodarone concentrations were measured at the time of defibrillation energy requirement determination. The mean defibrillation energy requirement before amiodarone therapy was 9.9 +/- 4.6 J. After initiation of amiodarone therapy, the mean defibrillation energy requirement increased to 13.7 +/- 5.6 J (P = 0.004). A linear relationship between the amiodarone (P = 0.02, r = 0.6), desethylamiodarone (P = 0.02, r = 0.6), and combined amiodarone-desethylamiodarone concentrations (P = 0.01, r = 0.6) and the defibrillation energy requirement was noted. Stepwise regression analysis demonstrated that the combined amiodarone-desethylamiodarone concentration was the only independent predictor of increase in the defibrillation energy requirement. CONCLUSION: Chronic oral amiodarone therapy increases the defibrillation energy requirement by approximately 62% in patients with an implantable defibrillator. The combined amiodarone-desethylamiodarone concentration is directly related to the increase in the defibrillation energy requirement.